The epidermis of human skin is a constantly regenerating tissue which gives rise to pathologic conditions characterized by altered rates of cellular proliferation. Cell proliferation kinetics have yielded valuable information on the pathophysiology of disease like psoriasis leading to more rational and improved forms of chemotherapy. Similar studies will be performed on other primary skin diseases as well as on malignancies that metastasize to the skin. A technic of multiple intradermal injections of radioactive compounds developed in our laboratories is used to study in vivo cellular kinetics, biochemical reactions and pharmacologic effects. The normal and abnormal biochemical pathways of DNA synthesis required for cell production will be studied, both in vivo and in vitro, in a spectrum of proliferative cutaneous diseases that include psoriasis, ichthyosis, pityriasis rubra pilari skin cancer and cutaneous metastases of internal malignancies taking advantage of their easy accessibility. The results of cellular kinetics will be used to help design programmed chemotherapy schedules for systemic malignancies. Athymic nude mice will be used to study the cell proliferation kinetics and growth characteristics of normal human epidermis and various benign and malignant skin diseases to establish a model for therapy. The pharmacology of chemotherapeutic drugs is extremely important for the therapy of diseases like psoriasis, pityriasis rubra pilaris, keratoacanthoma and malignancies. The mechanism of drug action in these skin diseases will be studied biochemically to find potential sites for specific drug attack. The use of methotrexate, its analogues and other chemotherapeutic drugs will continue to be studied intensively in psoriasis with the primary objective to develop a topically effective chemotherapeutic drug.